DESCRIPTION: Over 8 million people living with HIV/AIDS (PLWHA) in sub-Saharan Africa are taking antiretroviral therapy (ART). As HIV-related mortality declines, the population of HIV-infected persons over 50 years is rapidly increasing, and is expected to reach 10 million persons by 2040. The changing epidemic is motivating a public health paradigm shift towards a greater focus on improving long-term health. Data from resource-rich settings describe increased rates of atherosclerosis in HIV-infected versus HIV-uninfected persons. Root causes of the elevated risk arise from a multi-factorial process involving traditional cardiovascular risk factors, altere immune function, toxicity of ART, and the elevated inflammatory state associated with HIV infection. However, similar data on cardiovascular risk factors and outcomes are largely lacking from sub-Saharan Africa, which is home to 70% of HIV-infected persons globally. We will leverage a highly productive and established research infrastructure at a PEPFAR-supported, public HIV clinic in Mbarara, Uganda to enroll PLWHA on ART over 50 years of age, and an age and gender-matched HIV-uninfected comparison group sampled from an NIH- funded, population-based study of social networks in the hospital catchment area. We aim to measure the prevalence and correlates of atherosclerosis among PLWHA and age and gender-matched HIV- uninfected controls in rural, sub-Saharan Africa. Our outcomes of interest will be: measures of atherosclerosis, including: 1) carotid intima-media thickness, 2) ankle-brachial index, and 3) presence of q-waves on electrocardiogram Our exposures of interest will be: traditional cardiovascular disease risk factors (age, gender, family history of cardiovascular disease, smoking history, diet, activity, body mass index, prevalence of diabetes, and prevalence of hypertension) and HIV-related cardiovascular risk factors (nadir CD4 count, ART duration, gut and plasma microbiome composition, and markers of both immune activation and systemic inflammation). We combine a well-established research infrastructure in a rural, sub-Saharan African setting with world leaders in the study of cardiovascular disease epidemiology in HIV-infected populations. We will leverage these strengths to report atherosclerotic disease burden among PLWHA, as well as state-of- the-art molecular and immunologic testing for HIV-related risk factors. Results from this study will be used to apply for an NIH R01 application for longitudinal study of cardiovascular disease among PLWHA on ART in sub-Saharan Africa. Our over-arching aims include: 1) determination of high-burden health conditions for aging PLWHA on ART in sub-Saharan Africa, 2) identification of modifiable risk factors for prevention and interventions to improve cardiovascular outcomes, and 3) setting priorities for future research.